This proposal seeks to renew support for studies the long term goal of which exact definition of the molecular mechanism(s) by which bleomycin exerts its effects as an antitumor agent. For the period of requested support, it is proposed to: . study the orientation of BLM on the DNA duplex and the way in which double strand cleavage is mediated . analyze the role of metal ions in BLM ligation and DNA binding . study the effects of altered DNA structure on susceptibility to BLM cleavage . characterize the chemical nature of activated metallobleomycins and the way in which oxygen is transferred to olefinic substrates.